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News Article | April 4, 2017
Site: www.techtimes.com

It is an irrefutable fact that with the progression of age, the female body's ability to bear a child decreases. It has been a mystery why this may be the case — until now. A new study may finally be able to provide an answer to this question. A group of scientists from the University of Montreal Hospital Research Center conducted extensive research, which offers clues about female infertility. The study was conducted on older mice. Using state-of-the-art microscopic technology, researchers were able to determine a specific defect in the eggs belonging to the creatures. Scientists believe that this same defect may be present in the eggs of older human females, which causes complications while conceiving. Scientists carried out micromanipulations on mice eggs. The mice whose eggs were tested were aged 6 and 12 weeks, which is considered to be young for the creatures. The same procedure was followed for the eggs of 60-week mice, which is considered old. Researchers swapped the nuclei of the young eggs and placed them in the older eggs. They then observed the complications that arose following this change, which aimed to determine the cause of age-related infertility. The researchers found that the cell division process became distorted after the nuclei swap, which prohibited proper chromosome sharing to occur. This sharing is required for a pregnancy to initialize. "We found that the microtubules that orchestrate chromosome segregation during cell division behave abnormally in older eggs," stated professor Greg FitzHarris, a researcher at CRCHUM. He added that this abnormal movement of the microtubules is essentially what causes age-related infertility among females. "One of the main causes of female infertility is a defect in the eggs that causes them to have an abnormal number of chromosomes. These so-called aneuploid eggs become increasingly prevalent as a woman ages," explained FitzHarris. Previously, the scientific community believed that age-related infertility in women was caused by the improper working of the "glue" that kept chromosomes together. This theory is known as the "cohesion-loss" concept. However, the current research asserts that the study does not disprove the cohesion-loss theory. It only postulates that there could be another reason behind the phenomenon. The results of the latest study could pave the way for future treatments, which would perhaps address age-related infertility among women and aid in rejuvenating the eggs. However, researchers are quick to point out that such advancement would take several years as this study is just on a basic level. Many such similar studies would need to be conducted to learn more about these defects, before an effective treatment can be developed. The findings have been published in the journal Current Biology. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | March 20, 2017
Site: www.techtimes.com

Have you been advised by your doctor to take medicines for high blood pressure? Think twice. Do you really think you have high blood pressure? A new study states that about 20 percent of people who get treated for hypertension don't actually have the problem and need not resort to any medication. Blood pressure or BP is often described as the pressure that the blood exerts on the artery walls. It is measured from arm artery and expressed in two numbers, which are the systolic BP and the diastolic BP. When systolic pressure is lower than 140 mmHg and the diastolic pressure is less than 90 mmHg, the BP is considered normal. If a person's BP figure crosses the above stated numbers, then it is said the individual has high BP. According to Centers for Disease Control and Prevention (CDC), there are about 75 million American adults who suffer from high BP, which is one of every three adults. Treatment for this problem nearly costs the nation around $46 billion each year. A study conducted by researchers from University of Montreal Hospital Research Centre (CRCHUM) claims that over half the family doctors present in Canada continue to use manual devices to measure BP. The usage of this dated technology often leads to misdiagnosis of the numbers. "Clinicians should use automatic devices. They are more expensive but more precise because they take several measurements. Manual measurement is acceptable if it's properly done, but that's often not the case," said Janusz Kaczorowski, the lead author of the study. The automated device eliminates the chance of what is known as the white-coat syndrome. This syndrome refers to the additional stress or artificial BP the patient faces for being in a clinical environment. Due to this elimination, Kaczorowski believes that the right BP measurement could be taken. The study conducted by Kaczorowski and team was a web-based, cross-sectional survey. It was performed by researchers and professors with the aim of finding out techniques family physicians in Canada currently deploy to gauge BP. Participants were chosen through stratified random sampling of family physicians in Canada. The survey was distributed to them via e-mail. It was seen that out of the 769 respondents of the survey, 54.2 percent stated that they use manually run devices to measure BP. Only 43 percent of the total participants admitted using an automated device for gauging BP. The study surmised that in Canada, from an overall perspective, there are a high number of family physicians using electronic devices for BP measurement. This study has been published in the Canadian Family Physician. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | April 3, 2017
Site: www.medicalnewstoday.com

Infertility is recognized as a disease both in the U.S. and worldwide. It is clinically defined as the inability to get pregnant, or to successfully carry a pregnancy to term, after 1 year of unprotected sex. Approximately 1 in 8 U.S. couples are struggling to get pregnant or maintain a pregnancy. One third of infertility is typically attributed to men, another third to women, and a final third is thought to be caused by a combination of problems in both partners. Age is thought to play a crucial role in the ability to procreate. For a woman, the number of oocytes - that is, female egg cells before they fully develop into ova - naturally declines with age. Additionally, the quality of the eggs also decreases, particularly after a woman reaches the age of 37. New research, carried out by scientists at the University of Montreal Hospital Research Center (CRCHUM) in Canada, uses state-of-the-art microscopy technology in order to examine the genetics behind this aging process. The findings - published in the journal Current Biology - point to errors in chromosomal segregation as a new mechanism for explaining female age-related infertility. Eggs with an abnormal number of chromosomes are called aneuploid eggs, explain the researchers. As a woman ages, and particularly as she ages beyond 35 years, the number of aneuploid eggs increases. Until now, the widely accepted hypothesis for this increase in abnormal eggs stated that the glue-like substance - made of protein complexes called cohesins - that keeps the chromosomes unified starts to malfunction. This hypothesis has been called the "cohesion-loss" hypothesis. The new research does not contradict this theory, but it does find an additional problem. In the new study, the microtubules - which are small cylindrical structures within the cell that are responsible for cell movement and which organize themselves into a spindle - were found to be dysfunctional in older mice. Microtubules pull the chromosomes together around their spindle-like structure and "sort" them when it is time for the cells to divide. After cell division, microtubules send out these chromosomes to the opposite poles of the nucleus of the daughter cells in a process commonly known as chromosome segregation. In fact, Fitzharris says that "approximately 50 percent of the eggs of older females have a spindle with chaotic microtubule dynamics." The researchers learned this by micromanipulating the eggs of mice, a classic approach whereby the oocytes were swapped among young mice (aged between 6 and 12 weeks) and old ones (aged 60 weeks). "We swapped the nuclei of the young eggs with those of the old eggs and we observed problems in the old eggs containing a young nucleus," explains Shoma Nakagawa, a postdoctoral research fellow at CRCHUM and the Université de Montréal. "This shows that maternal age influences the alignment of microtubules independently of the age of the chromosomes contained in the nuclei of each egg." The findings also hold for humans, the authors explain. Chromosomal defects due to spindle malfunctioning occur in women as well, so age-related infertility does not seem to be caused by the age of the chromosomes themselves. In the future, the authors hope that their findings will help women to become pregnant despite their older age. "We are currently exploring possible treatments for eggs that might one day make it possible to reverse this problem and rejuvenate the eggs," says Fitzharris.


News Article | April 14, 2016
Site: www.biosciencetechnology.com

Catherine Aaron and Gabrielle Beaudry were 17 when they knocked on the door of the laboratory of Alex Parker, a neuroscience researcher at the University of Montreal Hospital Research Centre (CRCHUM). While students at Collège Jean-de-Brébeuf in Montreal, they were looking for a mentor for an after-school research project. Two and half years later, the results of this scientific adventure were published today in the Journal of Agricultural and Food Chemistry. "We wanted to test the effect of a natural product on a neurodegenerative disease such as Alzheimer's. Professor Parker had already discovered that sugar prevents the occurrence of amyotrophic lateral sclerosis (ALS) in an animal model of the disease, the C. elegans worm. That's how we got the idea of maple syrup, a natural sugar produced in Quebec," said Beaudry. Supervised by Ph.D. student Martine Therrien and Alex Parker, Aaron and Beaudry added maple syrup to the diet of these barely 1 mm-long nematodes. "We just gave them a supplement of maple syrup at various concentrations and compared with a control group that had a normal diet," said Aaron. "After twelve days, we counted under the microscope the worms that were moving and those that were paralyzed. The worms that had consumed the highest dose of syrup were much less likely to be paralyzed." Alex Parker's C. elegans worms are genetically modified to express a protein involved in ALS in motor neurons - TDP-43. "When they are adults, around 12 days, their motor neurons break down. Normally, at two weeks of life, 50 percent of the worms are completely paralyzed. But among those that received a diet enriched with 4 percent maple syrup, only 17 percent were paralyzed. We can therefore conclude that maple syrup protects neurons and prevents the development of amyotrophic lateral sclerosis in C. elegans worms," said Parker, a researcher at the CRCHUM and professor at the Faculty of Medicine, University of Montreal. How can we explain this dramatic effect? "Sugar is good for the nervous system. Diseased neurons require more energy to combat toxic proteins. But maple syrup is rich in polyphenols, powerful antioxidants found in certain foods. We isolated phenols contained in the maple syrup, and we showed that two polyphenols in particular, gallic acid and catechol, have a neuroprotective effect. In pure maple syrup, these polyphenols are found in low concentrations. Probably a combination of sugar and polyphenols prevents the occurrence of the disease in worms," said Therrien, a Ph.D. student at the CRCHUM. But don't go ahead and gorge yourself on maple syrup thinking it'll protect you against neurological diseases! "The life expectancy of C. elegans worms is only three weeks. They are spared the long-term toxic effects of sugar. Humans who consume comparable amounts of sugar risk developing chronic diseases such Type 2 diabetes and obesity," cautioned Parker. Amyotrophic lateral sclerosis is a rare neuromuscular disease that causes paralysis and death a few years after the onset of symptoms. So far, no cure is available for patients. This latest study on maple syrup and the C. elegans worm was conducted for educational purposes. Other studies by Alex Parker with C. elegans have led to the discovery of promising drugs, which will be tested in patients in a few years. Catherine Aaron and Gabrielle Beaudry won the Sanofi Biogenius Canada People's Choice Award - Quebec section - for this project in April 2014. Aaron is now a first-year medical student at the University of Montreal, and Beaudry studies psychology at the University of Sherbrooke.


News Article | February 27, 2017
Site: www.eurekalert.org

It is 2012 and Smiley, a young woman in her early 20s, lives in a single room occupancy (SRO) building in Vancouver. She wants to hang out with her friends in her room, where she feels safe, but the SRO only allows one visitor at a time. "I don't like it. It's their rules. It's really annoying," Smiley said. "It sucks, because I'm not a crackhead or a junkie. They shouldn't put me in places like that." Smiley has been diagnosed with psychosis, a mental disorder where people show signs of delusions and hallucinations. She's one of 17 young people between the ages of 18 to 24 in Metro Vancouver recruited for a study at the University of British Columbia. All participants have experienced symptoms of psychosis in the past three years. "Our study provides a window into what young people think about the mental health services they receive and what they feel helps and hinders their well-being," said lead author Shalini Lal, an assistant professor at the University of Montreal's school of rehabilitation and a researcher at the University of Montreal's Hospital Research Centre (CRCHUM). Lal conducted the study as part of her PhD work at UBC's faculty of medicine within the graduate programs of rehabilitation sciences. Through interview excerpts with the youth from November 2010 to March 2012, the study highlights the impacts of mental health services on these young people, including their interactions with psychiatrists, case managers, social workers and supports for housing, recreation, and employment. "Eliciting young people's feedback will lead to better planning and coordination of services that they will find engaging, meaningful and effective," said Lal. The study identifies many different types of supports the youth found helpful, including group therapy and positive interactions with peers and peer support workers. "The groups were very helpful for getting me to acknowledge that I actually had an illness," said Kevin, one of the youth. "(The peer support worker) explained that with the right combination of medications or professional help, you could actually treat the symptoms and live a normal life... a good role model to see that you could recover from it," said Jake, another youth involved in the study. Other types of support the youth identified as helpful were accompaniment to appointments, providing help in completing employment assistance forms and facilitating the process of returning to school. Youth also appreciated emotional support like signs of genuine kindness, hope and encouragement from service providers. "Even small gestures were seen as helpful, ones we may take for granted, like a care manager shaking their hand when they walked in the door," said Lal. "That gesture of respect has a lot of meaning for someone stigmatized by mental illness." When it came to hindrances, some youth felt pigeonholed by their mental illness, being offered services that didn't reflect an identity outside their disorder. A young man named Nelson, who had acting aspirations, told Lal about his disappointment when his job counselor connected him to a theatre company dedicated to "people affected by mental illness." "The most annoying thing is that everything is for mental health reasons and I just don't want this," he said. "If it's a film thing, I don't want it to be just for mentally ill, and just to address stuff like that. I want it to be, just normal." Darren, a 20-year-old living in a downtown youth shelter, didn't own a cellphone and could not receive calls directly from the shelter. His sense of independence and social life were negatively impacted by the shelter's rules of no Facebook access, which was his main way of staying in touch with friends and family. Lal said in some cases the youth also interacted with outreach workers online, which proved useful to providing support to people who would not otherwise receive it any other way. Some youth felt "ghettoized" by their housing situation, only being able to access SROs that housed many others living with mental health and substance abuse issues. Philip, a young man struggling with substance abuse in addition to his psychosis, said living in such an environment threatened his sobriety. "Every time you walk down the street you see someone on a crack pipe, a crystal meth pipe, a pot pipe or drinking alcohol every block you walk here," he said. "And it's nothing but trigger after trigger here, so it's not the right environment for people trying to stay sober. Just being around these kinds of people, it's not the right place for me." The last hindrance was how impersonal the youth felt some of their encounters could be with different support workers, including doctors or therapists. "It was always kind of detached, and I always felt like we were on the clock and not really supported to talk about things like that [relationships]... It just wasn't an environment where I felt comfortable with it," said Kevin. Lal said she has seen more funding and attention being paid to the mental health needs of young people in Canada, especially over the past five years. Lal also said more effort is needed in using tools and resources that cater to youth, including the use of technology to provide support. As well, different sectors of the community, including housing, employment and mental health, need to work more closely together, so people don't feel bounced around. "People often think that it's up to individuals alone to overcome adversity, to deal with a mental illness," Lal said. "For young people, their resiliency largely depends on their ability to navigate and negotiate towards resources, which are all too often substandard, inconsistent or not tailored to their needs." "We learned from this study that when services do match young people's needs and preferences, they can really make a positive impact on their well-being." The study, Impact of Mental Health Services on Resilience in Youth with First Episode Psychosis: A Qualitative Study, was published in print this year in Administration and Policy in Mental Health and Mental Health Services Research. Lal's co-authors are Michael Ungar at Dalhousie University, Ashok Malla at McGill University and Carl Leggo and Melinda Suto at UBC. The 17 youth involved in the study had an average age of 22 and 71 per cent were male. The youth were white, First Nations, Asian and Latin American. Seven of the youth had less than a high school education, five had completed high school, four had some university-level education, and one had completed a bachelor's degree. Names in this study were changed to protect the youths' identities and were chosen by the youth themselves. They are not available for interviews.


News Article | October 27, 2016
Site: www.eurekalert.org

Montreal, October 27, 2016. - You've tried all the diets. No matter: you've still regained the weight you lost, even though you ate well and you exercised regularly! This may be due to a particular enzyme in the brain: the alpha/beta hydrolase domain-6 enzyme, better known as ABHD6. A study published this week in Cell Reports demonstrates that when this enzyme is blocked in certain neurons of the mouse hypothalamus, it becomes impossible for them to lose weight, even if they adhere to an ideal regimen... ideal for mice that is! A research team at the University of Montreal Hospital Research Centre (CRCHUM) has generated genetically engineered mice, deprived of the ABHD6 enzyme in a localized area of the brain, namely in a specific population of hypothalamic neurons. Alexandre Fisette, postdoctoral researcher at CRCHUM and first author of the study, explains that, "under normal conditions of housing and food, these mice are identical to normal mice. However, when challenged, they are unable to adapt. They no longer consume food after a fast, they cannot maintain their body temperature during exposure to cold, and they are more susceptible to become obese when fed a high-fat diet. What's more, once they are obese and we try to make them lose weight by feeding them a normal diet, they do not lose weight." The researchers have discovered that this enzyme acts as a sort of switch for the body's adjustment to extremes. "It is a mechanism we had not suspected. Strikingly, the absence of one single enzyme within a precise region of the brain completely disrupts the normal metabolism and prevents the mice from losing weight," comments Thierry Alquier, CRCHUM researcher and professor at the University de Montréal. Is there an identical process taking place in humans? Thierry Alquier thinks that clinical studies will be required to find out. However, according to Alquier, "ABHD6 has a key role in the rebound effect that is often observed after a dietary regimen. People who experience difficulty losing weight might have a deficiency of this enzyme." Weight is controlled by several signals. Scientists have known for a long time that endocannabinoids - molecules secreted by the brain - are involved in the ingestion of nutrients and the expenditure of energy. The endocannabinoids stimulate appetite. Thus, this is an interesting area of exploration in the search for an appetite-suppressant drug. But all the products developed until now have been associated with serious side effects. The pursuit of the ABHD6 enzyme appears to be promising. In 2014, the team of Marc Prentki, another CRCHUM researcher, discovered that this enzyme breaks down endocannabinoids. Blocking ABHD6 in peripheral organs and adipose tissues protects against obesity and against type 2 diabetes. "We know today that ABHD6 plays a completely different role in certain neurons of the hypothalamus. Blocking the enzyme in this location promotes obesity, whereas blocking it elsewhere in the body has beneficial effects," emphasizes Stephanie Fulton, CRCHUM researcher and study co-author. Multiple signals and neuronal networks are involved in regulating the balance of energy so as to maintain a stable body weight. "We have shown the critical part played by the ABHD6 enzyme in preserving homeostasis in specific neurons of the hypothalamus. But we don't know what happens when we block the enzyme in the entire brain. This is what we are currently investigating in an ongoing study," the researcher explains. Many more years of research will be needed to develop an effective treatment for obesity. As science advances, we learn that weight management does indeed take place inside the head, but that it is not necessarily a question of lack of will. The study "a/b-Hydrolase Domain 6 in the Ventromedial Hypothalamus Controls Energy Metabolism Flexibility" was published on October 25, 2016, in Cell Report. Primary sponsoring institution: Instituts de recherche en santé du Canada (IRSC), (MOP115042), (MOP123280), and (MOP114974). The authors are grateful to the platform of rodent metabolomics and phenotyping of the CRCHUM and to the Montreal Diabetes Research Center for their support. To learn more, we invite you to read the study: http://dx.


News Article | October 29, 2016
Site: www.sciencedaily.com

You've tried all the diets. No matter: you've still regained the weight you lost, even though you ate well and you exercised regularly! This may be due to a particular enzyme in the brain: the alpha/beta hydrolase domain-6 enzyme, better known as ABHD6. A study published this week in Cell Reports demonstrates that when this enzyme is blocked in certain neurons of the mouse hypothalamus, it becomes impossible for them to lose weight, even if they adhere to an ideal regimen… ideal for mice that is! A research team at the University of Montreal Hospital Research Centre (CRCHUM) has generated genetically engineered mice, deprived of the ABHD6 enzyme in a localized area of the brain, namely in a specific population of hypothalamic neurons. Alexandre Fisette, postdoctoral researcher at CRCHUM and first author of the study, explains that, "under normal conditions of housing and food, these mice are identical to normal mice. However, when challenged, they are unable to adapt. They no longer consume food after a fast, they cannot maintain their body temperature during exposure to cold, and they are more susceptible to become obese when fed a high-fat diet. What's more, once they are obese and we try to make them lose weight by feeding them a normal diet, they do not lose weight." The researchers have discovered that this enzyme acts as a sort of switch for the body's adjustment to extremes. "It is a mechanism we had not suspected. Strikingly, the absence of one single enzyme within a precise region of the brain completely disrupts the normal metabolism and prevents the mice from losing weight," comments Thierry Alquier, CRCHUM researcher and professor at the University de Montréal. Is there an identical process taking place in humans? Thierry Alquier thinks that clinical studies will be required to find out. However, according to Alquier, "ABHD6 has a key role in the rebound effect that is often observed after a dietary regimen. People who experience difficulty losing weight might have a deficiency of this enzyme." Weight is controlled by several signals. Scientists have known for a long time that endocannabinoids -- molecules secreted by the brain -- are involved in the ingestion of nutrients and the expenditure of energy. The endocannabinoids stimulate appetite. Thus, this is an interesting area of exploration in the search for an appetite-suppressant drug. But all the products developed until now have been associated with serious side effects. The pursuit of the ABHD6 enzyme appears to be promising. In 2014, the team of Marc Prentki, another CRCHUM researcher, discovered that this enzyme breaks down endocannabinoids. Blocking ABHD6 in peripheral organs and adipose tissues protects against obesity and against type 2 diabetes. "We know today that ABHD6 plays a completely different role in certain neurons of the hypothalamus. Blocking the enzyme in this location promotes obesity, whereas blocking it elsewhere in the body has beneficial effects," emphasizes Stephanie Fulton, CRCHUM researcher and study co-author. Multiple signals and neuronal networks are involved in regulating the balance of energy so as to maintain a stable body weight. "We have shown the critical part played by the ABHD6 enzyme in preserving homeostasis in specific neurons of the hypothalamus. But we don't know what happens when we block the enzyme in the entire brain. This is what we are currently investigating in an ongoing study," the researcher explains. Many more years of research will be needed to develop an effective treatment for obesity. As science advances, we learn that weight management does indeed take place inside the head, but that it is not necessarily a question of lack of will.


News Article | April 13, 2016
Site: www.sciencedaily.com

Catherine Aaron and Gabrielle Beaudry were 17 when they knocked on the door of the laboratory of Alex Parker, a neuroscience researcher at the University of Montreal Hospital Research Centre (CRCHUM). While high school students they were looking for a mentor for an after-school research project. Two and half years later, the results of this scientific adventure were published today in the Journal of Agricultural and Food Chemistry.


News Article | September 19, 2016
Site: www.biosciencetechnology.com

Discovery of a novel, advanced technique to identify the rare cells where human immunodeficiency virus (HIV) hides in patients taking antiretroviral therapy (ART). This is an important step forward in the search for a HIV/AIDS cure. Why wake up the virus? To better kill it, of course. A team from the University of Montreal Hospital Research Centre (CRCHUM) has taken an important step forward in the search for a HIV/AIDS cure. The laboratory of Dr. Daniel Kaufmann has developed a highly accurate technique for detecting the rare cells that hide the virus and prevent current therapies from curing HIV infection. "We can wake up the virus and then find the rare cells that have been hiding it at very low numbers, a limit of one cell in a million. This is an unprecedented level of accuracy, which opens the door to individualized monitoring of HIV-positive patients and could facilitate the development of personalized treatments," said Dr. Kaufmann, senior author of a study on the subject published in a featured article in the current issue of Cell Host & Microbe. HIV reservoirs are cells and tissues in which the virus persists despite ART. The virus predominantly lives and replicates in a particular type of white blood cell, CD4+ T lymphocytes. While antiretroviral drugs are generally successful in controlling the viral load in infected individuals, preventing the progression to acquired immunodeficiency syndrome (AIDS), some viruses remain hidden for years and can be reactivated if patients stop their treatment. "CD4+ T lymphocyte populations are highly variable. To develop new, targeted treatments to eliminate these residual infected cells, we need to find exactly where in the CD4 T lymphocyte population the virus hides. Our research has uncovered these HIV hiding places. We were able to identify and quantify the cells containing hidden virus and then test drugs to wake up HIV," said Kaufmann, who is a researcher and infectious disease specialist at the University of Montreal Hospital Centre (CHUM). His team has developed an innovative technique for detecting these reservoirs – a way of taking a "photo" of each individual cell hiding the virus – a significant breakthrough, as this approach is 1,000 times more accurate than current technologies. Once the HIV hiding places are found, the researchers can use a "shock and kill" strategy to eliminate the virus in two stages. Firstly, the HIV must be woken up from its dormant state in the cells. The virus then becomes visible to the immune system or drugs that can eliminate it. Professor Kaufmann's team analyzed the blood of 30 patients infected with HIV, both before patients started treatment and after they received ART. "We were able to detect the virus in CD4+ T lymphocytes in almost all of the patients we analyzed," said Amy Baxter, a postdoctoral fellow at the CRCHUM and first author of the study. The researchers then tested two so-called latency reversal drugs: bryostatin and a derivative of ingenol. These drugs were developed to fight cancer, but might also be used against HIV. "While our studies were conducted in the laboratory, a clinical trial would involve using such drugs to wake up the virus while the patient continues taking ART to ensure that the reactivated virus can not infect other cells," explained Dr. Kaufmann. "In the laboratory we found that the two drugs wake up different populations of CD4+ T lymphocytes, thus waking up different reservoirs. The ingenol derivative activates a population called central memory cells. These cells can live for years in patients, all the while hiding the virus. Therefore, it is particularly important to target these reservoirs," noted Baxter. At first sight it appears as though the virus hides in similar places in different patients. However, Dr. Kaufmann's team has revealed that there is also large variability from one patient to another. "We may have to adjust the treatment for individual patients, depending on the specific HIV hiding places in each case. To minimize the virus pools, we will have to assess patients and tailor the "shock and kill" therapies to their profiles," said Dr. Kaufmann. Before arriving at a potential treatment for humans, the researchers are planning to evaluate the effectiveness of new drugs to awaken similar virus reservoirs in monkeys and determine where the virus is hidden. If the drugs are well tolerated, clinical trials will begin in a few years. After 30 years of research to cure HIV infection and AIDS, this opens a whole new avenue in understanding how scientists could track and find infected cells, then wake up and kill the virus hiding deep inside.


Sikora J.,CRCHUM | Orlov S.N.,CRCHUM | Orlov S.N.,University of Montréal | Furuya K.,Nagoya University | And 2 more authors.
Blood | Year: 2014

The hypothesis that regulated ATP release from red blood cells (RBCs) contributes to nitric oxide-dependent control of local blood flow has sparked much interest in underlying release mechanisms. Several stimuli, including shear stress and hypoxia, have been found to induce significant RBC ATP release attributed to activation of ATP-conducting channels. In the present study, we first evaluated different experimental approaches investigating stimulated RBC ATP release and quantifying hemolysis. We then measured ATP and free hemoglobin in each and every RBC supernatant sample to directly assess the contribution of hemolysis to ATP release. Hypotonic shock, shear stress, and hypoxia, but not cyclic adenosine monophosphate agonists, significantly enhanced ATP release. It tightly correlated, however, with free hemoglobin in RBC supernatants, indicating that lysis was responsible for most, if not all, ATP release. Luminescence ATP imaging combined with simultaneous infrared cell imaging showed that ATP was released exclusively from lysing cells with no contribution from intact cells. In summary, with all stimuli tested, we found no evidence of regulated ATP release from intact RBCs other than by cell lysis. Such a release mechanism might be physiologically relevant in vivo, eg, during exercise and hypoxia where intravascular hemolysis, predominantly of senescent cells, is augmented. © 2014 by The American Society of Hematology.

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